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OBJECTIVE: The purpose of this study was to evaluate the applicability of visual evoked potentials (VEP) for intraoperative visual pathway monitoring in epilepsy surgery of the posterior hemispheric quadrant (PHQ) and to correlate it with post-operative visual field status. METHODS: VEP monitoring was performed in 16 patients (12 females, 7 children). Flash-induced VEP were recorded with strip electrodes from the banks of the calcarine cortex. Latency and amplitude of the first component of VEP (V1-lat, V1-amp) were monitored. Evaluation of the visual field was performed pre- and post-operatively in all patients. RESULTS: All procedures were successfully completed without adverse events. In 10 patients the strip covered both the inferior and superior calcarine banks, while only one bank was sampled in 6 cases (inferior in 4, superior in 2). Considering one of the two calcarine banks, at the end of the resection VEP had disappeared in 4 patients, whereas a decrease >33.3% in 4 and <20% of V1-amp was recorded in 5 and in 4 cases respectively. The percentage of V1-amp reduction was significantly higher for the patients who experienced a post-operative visual field reduction (p < 0.001). Post-operative visual field deficits were found in patients presenting a reduction >33.3% of V1-amp. CONCLUSIONS: VEP monitoring is possible and safe in epilepsy surgery under general anesthesia. SIGNIFICANCE: Intraoperative recording of VEP from the banks of the calcarine cortex allows monitoring the integrity of post-geniculate visual pathways during PHQ resections for epilepsy and it is pivotal to prevent disabling visual field defects, including hemianopia and inferior quadrantanopia.
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OBJECTIVE: To assess seizure and developmental outcomes, their predictors, and complications in 160 children who, between 1998 and 2022, underwent surgery for lesional epilepsy with curative intent before the age of 3 years. To compare trends in epilepsy surgery in this age group before and after the year 2014. METHODS: Retrospective multicenter study. Descriptive and univariate analyses, and multivariable models for all outcomes. RESULTS: These 160 patients (76 F; 47.5%) underwent 169 surgeries (age at surgery 20.4 ± 9.4 months). At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were in Engel class I, 106 (66.2%) of whom were in Engel class Ia. Antiseizure medications were stopped in 84 patients (52.5%). Complications requiring reoperations were observed in 16 patients (10%; 9.5% of surgeries) and unexpected permanent deficits in 12 (7.5%; 7.1% of surgeries). Postoperative cognitive functions remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Multivariable analyses showed that the probability of achieving Engel class Ia was lower when the duration of epilepsy was longer, patients underwent preoperative video-EEG, and unexpected postoperative permanent deficits occurred. Cognitive improvement after surgery was associated with lower preoperative seizure frequency, better preoperative developmental level, and a longer postoperative follow-up. FCDII and tumors were the histopathologies carrying a higher probability of achieving seizure freedom, while polymicrogyria was associated with a lower probability of cognitive improvement. The number of patients operated on after 2014 was higher than before (61.3% vs. 38.7%), with stable outcomes. SIGNIFICANCE: Epilepsy surgery is effective and safe in infants and toddlers, although the complication rate is higher than seen in older patients. Shorter duration of epilepsy, lower seizure frequency, no need for video-EEG, tumors, and some malformations of cortical development are robust predictors of seizure and cognitive outcome that may be exploited to increase earlier referral. PLAIN LANGUAGE SUMMARY: This study analyzed the results of epilepsy surgery in 160 children who had been operated on before the age of 3 years at four Italian centers between 1998 and 2022. At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were free from disabling seizures, of which 106 (66.2%) were completely seizure-free since surgery. Major surgical complications occurred in 28 patients (17.5%), which is higher than observed with epilepsy surgery in general, but similar to hemispheric/multilobar surgery. Postoperative cognitive function remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Epilepsy surgery is effective and safe in infants and toddlers.
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Epilepsia , Procedimentos Neurocirúrgicos , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Lactente , Estudos Retrospectivos , Pré-Escolar , Epilepsia/cirurgia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Procedimentos Neurocirúrgicos/efeitos adversosRESUMO
Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 µg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2ß: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.
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Administração Intravenosa , Povidona , Quercetina , Solubilidade , Água , Animais , Quercetina/farmacocinética , Quercetina/análogos & derivados , Quercetina/administração & dosagem , Quercetina/química , Ratos , Masculino , Água/química , Povidona/química , Compostos de Benzalcônio/farmacocinética , Compostos de Benzalcônio/química , Ratos WistarRESUMO
OBJECTIVE: The objective of this study was to identify risk factors associated with surgery-related neurological morbidity in patients with drug-resistant epilepsy undergoing suprasylvian operculoinsular resections. As secondary outcomes, we also analyzed the risk factors for ischemic lesion (IL) of corona radiata and seizure recurrence. METHODS: A retrospective analysis was conducted on a cohort of patients who underwent suprasylvian operculoinsular resections for drug-resistant epilepsy. The association of several presurgical, surgical, and postsurgical factors with both primary (persistent neurological deficits) and secondary (structural abnormalities on postoperative magnetic resonance imaging [MRI] and seizure recurrence) postoperative outcomes was investigated with univariate and multivariate statistical analysis. RESULTS: The study included a total of 65 patients; 46.2% of patients exhibited postoperative neurological deficits, but only 12.3% experienced persistent deficits. On postoperative MRI, IL in the corona radiata and corticospinal tract Wallerian degeneration (CSTWd) were seen in 68% and 29% of cases, respectively. Only CSTWd was significantly associated with persistent neurological deficits (relative risk [RR] = 2.6). Combined operculoinsular resection (RR = 3.62) and surgery performed on the left hemisphere (RR = .37) were independently associated with IL in the corona radiata. Variables independently associated with CSTWd were the presence of malacic components in the IL (RR = 1.96), right central operculum resection (RR = 1.79), and increasing age at surgery (RR = 1.03). Sixty-two patients had a postoperative follow-up > 12 months (median = 56, interquartile range = 30.75-73.5), and 62.9% were in Engel class I at last outpatient control. The risk of seizure recurrence was reduced by selective opercular resection (RR = .25) and increased by the histological diagnosis of aspecific gliosis (RR = 1.39). SIGNIFICANCE: This study provides insights into the risk factors associated with surgery-related neurological morbidity, as well as further evidence on the postoperative occurrence of subcortical injury and seizure recurrence in epileptic patients undergoing suprasylvian operculoinsular resections. The findings highlighted in this study may be useful to better understand the processes supporting the increased surgical risk in the operculoinsular region.
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Epilepsia Resistente a Medicamentos , Epilepsia , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Epilepsia/etiologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia Resistente a Medicamentos/complicações , Convulsões/complicações , Imageamento por Ressonância Magnética/métodos , Morbidade , Eletroencefalografia/efeitos adversosRESUMO
PURPOSE: Several surgical options are available for treating hypothalamic hamartoma-related epilepsy but their respective efficacy and safety profiles are poorly defined. METHODS: A literature search identified English-language articles reporting series of patients (minimum 3 patients with a follow-up ≥12 months) operated on by either microsurgery, endoscopic surgery, radiosurgery, radiofrequency thermocoagulation or laser interstitial thermal therapy for hypothalamic hamartoma-related epilepsy. The unit of analysis was each selected study. Pooled rates of seizure freedom and of neurological and endocrinological complications were analyzed using meta-analysis to calculate both fixed and random effects. The results of meta-analyses were compared. RESULTS: Thirty-nine studies were included. There were 568 and 514 participants for seizure outcome and complication analyses, respectively. The pairwise comparison showed that: i) the proportion of seizure-free cases was significantly lower for radiosurgery as compared to microsurgery, radiofrequency thermocoagulation and laser ablation, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation; ii) the proportion of permanent hypothalamic dysfunction was significantly higher for microsurgery as compared to all other techniques, and significantly lower for endoscopic surgery as compared to radiofrequency thermocoagulation and laser ablation; iii) the incidence of permanent neurological disorders was significantly higher for microsurgery as compared to endoscopic surgery, radiosurgery and radiofrequency thermocoagulation, and significantly lower for radiosurgery as compared to laser ablation. CONCLUSIONS: Minimally invasive surgical techniques, including endoscopic surgery, radiofrequency thermocoagulation and laser ablation, represent an acceptable compromise between efficacy and safety in the treatment of hypothalamic hamartoma-related epilepsy. Microsurgery and radiosurgery should be considered in carefully selected cases.
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Epilepsia , Hamartoma , Doenças Hipotalâmicas , Radiocirurgia , Humanos , Epilepsia/cirurgia , Epilepsia/complicações , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/cirurgia , Hamartoma/complicações , Hamartoma/cirurgia , Convulsões/cirurgia , Convulsões/complicações , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Resultado do Tratamento , Imageamento por Ressonância MagnéticaRESUMO
The Paediatric Committee of the European Medicines Agency encourages research into medicinal products for children, in particular, the development of an age-appropriate formulation of captopril is required in the cardiovascular therapeutic area. The aim of this study was the development of a liquid formulation using nanoparticles based only on chitosan and cellulose acetate phthalate containing captopril for the treatment of hypertension, heart failure and diabetic nephropathy in paediatric patients. Nanoparticles were prepared by a nanoprecipitation method/dropping technique without using surfactants, whose use can be associated with toxicity. A range of different cellulose to chitosan weight ratios were tested. A good encapsulation efficiency (61.0 ± 6.5%) was obtained when a high chitosan concentration was used (1:3 ratio); these nanoparticles (named NP-C) were spherical with a mean diameter of 427.1 ± 32.7 nm, 0.17 ± 0.09 PDI and +53.30 ± 0.95 mV zeta potential. NP-C dispersion remained stable for 28 days in terms of size and drug content and no captopril degradation was observed. NP-C dispersion released 70% of captopril after 2 h in pH 7.4 phosphate buffer and NP-C dispersion did not have a cytotoxicity effect on neonatal human fibroblasts except at the highest dose tested after 48 h. As a result, chitosan/cellulose nanoparticles could be considered a suitable platform for captopril delivery in paediatrics for preparing solid/liquid dosage forms.
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The aim of epilepsy treatment is to achieve seizure freedom. Surgery is often still considered a late option when pharmacological treatments have failed and epilepsy has become drug-resistant. We analyse the clinical features and surgical outcome in patients who underwent surgery without experiencing drug-resistance comparing with those observed in patients who became drug-resistant. Two-hundred and fifty patients with symptomatic focal epilepsy (12.1% of patients who underwent surgery at the "Claudio Munari" Epilepsy Surgery Center) were selected on the basis of initial period of seizure freedom and followed-up for at least 12 months. Patients were divided into two groups: those who underwent surgery during the initial period of seizure freedom (n = 74), and those who underwent surgery after an initial seizure-free period followed by drug-resistance (n = 176). Outcomes were significantly better in non-drug-resistant patients (p < 0.001), all of whom had Engel class Ia or Ic. In the drug-resistant group, 136 patients (77.3%) had class Ia or Ic. The median post-operative follow-up was respectively 75.0 and 84.0 months. Epilepsy surgery is a successful treatment, especially for non-drug-resistant patients with focal epilepsy with structural etiology. The timing of surgery affects the outcomes, and "early" surgery should be preferred to prevent likely drug-resistance and to improve prognosis.
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The current study, conceived with the contribution of the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) and the Epilepsy Study Group of the Italian Neurological Society (SIN), aimed to assess potential physician-related barriers to refer subjects for epilepsy surgery. All the members of SIN and LICE were invited by email to complete a 28-item online questionnaire. The survey items included: (1) individual and medical practice characteristics, (2) knowledge of current indications to select candidates for epilepsy surgery, (3) factors potentially affecting the attitude toward epilepsy surgery. Overall, 210 physicians completed the survey. More than half (63.3%) of the participants showed proper knowledge of the ILAE drug-resistance. Definition and almost two-thirds of them (71.9%) considered themselves adequately informed about indications, risks, and benefits of epilepsy surgery. Surgery was regarded as a valid option to be used as early as possible by 84.8% of the interviewees, and 71% of them estimated its complication rate to be low. However, more than half (63%) of the respondents reportedly referred patients for surgery only after the failure of 3-5 antiseizure medications. Overestimation of risks/complications of surgery and inadequate healthcare resources were identified as the main factor contrasting the patient referral for surgery by 43% and 40.5% of the participants, respectively. In conclusion, this survey confirms the existence of knowledge gap within both physicians and the healthcare system, as well as an educational need regarding epilepsy surgery. Further researches are warranted to define learning outcomes and optimize educational tools.
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Epilepsia , Médicos , Epilepsia/tratamento farmacológico , Epilepsia/cirurgia , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Neurologistas , Inquéritos e QuestionáriosRESUMO
PURPOSE: This study aimed to identify risk factors of postoperative seizure outcome in a consecutive cohort of patients operated on for TSC-related focal epilepsy, by evaluating several presurgical and surgical variables, including also MRI-visible brain abnormalities other than cortical tubers. METHODS: This retrospective study included 51 patients surgically treated for drug-resistant focal epilepsy with a histological diagnosis of cortical tuber and followed for at least 12 months postoperatively. We investigated the association between several potentially explanatory variables and seizure outcome by univariate and multivariate analysis in the whole cohort and in the subgroups of patients with single and multiple tubers, respectively. RESULTS: The median postoperative follow-up was 115 months (IQR 63-168) and 54.9% of patients were in Engel's class I at final control. In the whole cohort, variables independently associated with an unfavorable seizure outcome (Engel's classes II-IV) were: preoperative non-focal interictal EEG (RR 5, CI 2.46-6.39), presence of sub-ependymal nodules (SEN) (RR 3.53, CI 1.71-4.56) and seizure onset before the first year of age (RR 3.56, CI 0.91-6.89). Non-focal interictal EEG was independently associated with an unfavorable outcome also in the subgroup of patients with multiple tubers (RR 4.34, CI 2.23-5.37), while the presence of SEN (p=0.0221) and of extra-central nervous system lesions (p= 0.0152) predicted an unfavorable seizure outcome in patients with a single tuber. CONCLUSION: Surgery represents an effective option for seizure control in patients with TSC-related epilepsy. The identification of preoperative risk factors for seizure outcome could be helpful for optimizing patients' selection for surgery and pre-surgical counseling.
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Epilepsia Resistente a Medicamentos , Epilepsias Parciais , Epilepsia , Esclerose Tuberosa , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia/efeitos adversos , Epilepsias Parciais/complicações , Epilepsia/complicações , Epilepsia/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Convulsões/complicações , Convulsões/cirurgia , Resultado do Tratamento , Esclerose Tuberosa/complicações , Esclerose Tuberosa/cirurgiaRESUMO
OBJECTIVE: Lateral periinsular hemispherotomy (LPH) and vertical parasagittal hemispherotomy (VPH) are the most popular disconnective techniques for intractable epilepsies associated with unilateral hemispheric pathologies. The authors aimed to investigate possible differences in seizure outcome and complication rates between patients who underwent LPH and VPH. METHODS: A comprehensive literature search of PubMed and Embase identified English-language articles published from database inception to December 2019 that reported series (minimum 12 patients with follow-up ≥ 12 months) on either LPH or VPH. Pooled rates of seizure freedom and complications (with a particular focus on hydrocephalus) were analyzed using meta-analysis to calculate both fixed and random effects. Heterogeneity (Cochran's Q test) and inconsistency (fraction of Q due to actual heterogeneity) were also calculated. RESULTS: Twenty-five studies were included. Data from 825 patients were available for seizure outcome analysis (583 underwent LPH and 242 underwent VPH), and data from 692 patients were available for complication analysis (453 underwent LPH and 239 underwent VPH). No differences were found in the pooled rates of Engel class I seizure outcome between patients who underwent LPH (80.02% and 79.44% with fixed and random effects, respectively) and VPH (79.89% and 80.69% with fixed and random effects, respectively) (p = 0.953). No differences were observed in the pooled rates of shunted hydrocephalus between patients who underwent LPH (11.34% and 10.63% with fixed and random effects, respectively) and VPH (11.07% and 9.98% with fixed and random effects, respectively) (p = 0.898). Significant heterogeneity and moderate inconsistency were determined for hydrocephalus occurrence in patients who underwent both LPH and VPH. CONCLUSIONS: LPH and VPH techniques present similar excellent seizure outcomes, with comparable and acceptable safety profiles.
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The management of drug-resistant patients with focal epilepsy is often challenging. Surgery is recognised as a useful and effective treatment option. The identification of the epileptogenic zone relies on the integration of clinical, neurophysiological, and neuroimaging findings. The role of non-invasive functional neuroimaging techniques has been reported to add diagnostic accuracy to first-line evaluations, avoiding invasive presurgical examinations in selected cases. In this view, we report the case of a 16-year-old male suffering from drug-resistant focal epilepsy with episodes rarely evolving to a bilateral tonic-clonic seizure. Conventional 1.5T and 3T MRI were considered uninformative. Based on electro-clinical data, focal cortical dysplasia was suspected. The epileptogenic zone was identified with the integration of further non-invasive functional neuroimaging techniques ([18F]-fluorodeoxyglucose positron emission tomography and arterial spin labelling), where electrical source imaging played the main role. All techniques pointed towards a cortical region, where a 7T brain MRI identified a signal alteration consistent with focal cortical dysplasia. A tailored resection of the lesion located in the inferior frontal sulcus was performed, guided by intraoperative electrocorticography (strip and depth electrodes). Postoperative seizure freedom was achieved. The histopathology confirmed the suspicion of focal cortical dysplasia type IIa. With this case report, we highlight the importance of a multimodal approach in the presurgical evaluation of candidates for epilepsy surgery, which, in selected cases, may allow invasive procedures, such as stereo-EEG, to be avoided in the investigation of the epileptogenic zone. Moreover, we underline the pivotal role of EEG source imaging, especially when focal cortical dysplasia is suspected.
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Epilepsias Parciais , Adolescente , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical , Malformações do Desenvolvimento Cortical do Grupo I , Preparações Farmacêuticas , Resultado do TratamentoRESUMO
Hemispheric surgery is an effective and cost-effective option for hemispheric epilepsy. Data specifically focusing on very early infancy are scant. In our study, we report the results of hemispheric surgery in children under three years of age, along with clinical, neuroradiological and EEG features, from two Italian epilepsy surgery centres. After reviewing our epilepsy surgery databases (2008-2018), we identified 14 patients (seven males) submitted to hemispheric surgery, under three years (range: 2-29 months), with a follow-up of at least 12 months. No deaths occurred, and surgical complications were observed in 3/17 procedures. At final follow-up visit (mean: 30.8 months; range: 12-90), 10/14 patients (71.4%) achieved Engel Class I (eight Class 1A, one Class 1B, and one Class 1C). Antiepileptic drugs were completely discontinued in three and reduced in eight, thus a significant decrease in drug regimen after surgery was achieved in 11/14 patients (78.6%). Before surgery, severe developmental delay was present in 10 patients, moderate in two and mild in two. At the last follow-up visit, the degree of developmental delay changed from severe to moderate in five patients, remained unchanged in six cases (four severe and two moderate), and changed from mild to moderate in two following surgery. In many cases, hemispheric surgery in children under three years is effective in achieving seizure freedom or reducing seizure frequency, with the possibility of simplifying complex drug regimens. Moreover, it appears to be a safe and well tolerated procedure, leading to improvement in cognition and posture.
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Epilepsia , Pré-Escolar , Eletroencefalografia , Epilepsia/cirurgia , Feminino , Seguimentos , Hemisferectomia , Humanos , Masculino , Preparações Farmacêuticas , Estudos Retrospectivos , Convulsões/cirurgia , Resultado do TratamentoRESUMO
INTRODUCTION: Semiology and anatomo-electroclinical correlations remain invaluable for maintaining the level of excellence in temporal lobe epilepsy (TLE) surgery, in parallel to the constantly evolving technical progress. The aim of this study was to address semiological frequent and not so frequent signs, rarities and red flags in a long follow-up surgical series of patients suffering from TLE. METHODS: Patients operated within the boundaries of the TL at our center, with presurgical video-EEG recorded seizures and seizure free after a postoperative follow-up of at least 24â¯months were included. Ictal semiology was systematically described and new red flags were explored by comparing with a second group of patients with the same inclusion criteria but whose outcome had been unfavorable (Engel II-IV). RESULTS: Sixty-two patients were included, 46 seizure free and 16 with outcome Engel II-IV. Most seizure-free patients had a classical semiological presentation including aura (69.6%, abdominal the most frequent), followed by loss of responsiveness (90.2%) oral automatisms (90.7%), ipsilateral gestural automatisms (53.5%), contralateral upper limb dystonia (37.5%) or immobility (39.1%), and early ipsilateral non-versive head orientation (33.3%). More infrequent presentations were also present in the group of seizure-free patients: ictal language disturbance (13%), maintenance of responsiveness during seizures (9.8%), and contralateral rhythmic non manipulative automatism (6.9%). The presence of an isolated viscerosensory and/or psychic aura was significantly more frequent in the seizure-free group (pâ¯=â¯0.017), as well as oroalimentary automatisms (pâ¯=â¯0.005). Two signs were only present in the group with outcome Engel II-IV, constituting possible red flags (0.06â¯<â¯pâ¯<â¯0.07): inferior limbs stepping-like automatisms and postictal dysarthria. CONCLUSION: An adequate clinical exam during seizures and a careful analysis of video recordings allow to recognize infrequent but well-characterized ictal signs that are part of the range of semiology in TLE, together with the most frequent and classical ictal presentations. Special attention to the localization hypothesis must be paid in the absence of oroalimentary automatisms or when the signs classified as possible red flags emerge.
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Epilepsia do Lobo Temporal , Automatismo , Eletroencefalografia , Epilepsia do Lobo Temporal/complicações , Epilepsia do Lobo Temporal/diagnóstico , Lateralidade Funcional , Humanos , ConvulsõesRESUMO
OBJECTIVE: Drug-resistant epilepsy (DRE) during the first few months of life is challenging and necessitates aggressive treatment, including surgery. Because the most common causes of DRE in infancy are related to extensive developmental anomalies, surgery often entails extensive tissue resections or disconnection. The literature on "ultra-early" epilepsy surgery is sparse, with limited data concerning efficacy controlling the seizures, and safety. The current study's goal is to review the safety and efficacy of ultra-early epilepsy surgery performed before the age of 3 months. METHODS: To achieve a large sample size and external validity, a multinational, multicenter retrospective study was performed, focusing on epilepsy surgery for infants younger than 3 months of age. Collected data included epilepsy characteristics, surgical details, epilepsy outcome, and complications. RESULTS: Sixty-four patients underwent 69 surgeries before the age of 3 months. The most common pathologies were cortical dysplasia (28), hemimegalencephaly (17), and tubers (5). The most common procedures were hemispheric surgeries (48 procedures). Two cases were intentionally staged, and one was unexpectedly aborted. Nearly all patients received blood products. There were no perioperative deaths and no major unexpected permanent morbidities. Twenty-five percent of patients undergoing hemispheric surgeries developed hydrocephalus. Excellent epilepsy outcome (International League Against Epilepsy [ILAE] grade I) was achieved in 66% of cases over a median follow-up of 41 months (19-104 interquartile range [IQR]). The number of antiseizure medications was significantly reduced (median 2 drugs, 1-3 IQR, p < .0001). Outcome was not significantly associated with the type of surgery (hemispheric or more limited resections). SIGNIFICANCE: Epilepsy surgery during the first few months of life is associated with excellent seizure control, and when performed by highly experienced teams, is not associated with more permanent morbidity than surgery in older infants. Thus surgical treatment should not be postponed to treat DRE in very young infants based on their age.
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Epilepsia Resistente a Medicamentos , Epilepsia , Malformações do Desenvolvimento Cortical , Idoso , Epilepsia Resistente a Medicamentos/cirurgia , Eletroencefalografia , Epilepsia/cirurgia , Estudos de Viabilidade , Humanos , Lactente , Estudos Retrospectivos , Resultado do TratamentoRESUMO
In 2009, the Commission for Epilepsy Surgery of the Italian League Against Epilepsy (LICE) conducted an overview about the techniques used for the pre-surgical evaluation and the surgical treatment of epilepsies. The recognition that, in selected cases, surgery can be considered the first-line approach, suggested that the experience gained by the main Italian referral centers should be pooled in order to provide a handy source of reference. In light of the progress made over these past years, some parts of that first report have accordingly been updated. The present revision aims to harmonize the general principles regulating the patient selection and the pre-surgical work-up, as well as to expand the use of epilepsy surgery, that still represents an underutilized resource, regrettably. The objective of this contribution is drawing up a methodological framework within which to integrate the experiences of each group in this complex and dynamic sector of the neurosciences.
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Epilepsia , Neurociências , Epilepsia/cirurgia , Humanos , Procedimentos Neurocirúrgicos , Seleção de Pacientes , Encaminhamento e ConsultaRESUMO
OBJECTIVE: To evaluate the applicability of corticocortical evoked potentials (CCEP) for intraoperative monitoring of the language network in epilepsy surgery under general anesthesia. To investigate the clinical relevance on language functions of intraoperative changes of CCEP recorded under these conditions. METHODS: CCEP monitoring was performed in 14 epileptic patients (6 females, 4 children) during resections in the left perisylvian region under general anesthesia. Electrode strips were placed on the anterior language area (AL) and posterior language area (PL), identified by structural and functional magnetic resonance imaging. Single-pulse electric stimulations were delivered to pairs of adjacent contacts in a bipolar fashion. During resection, we monitored the integrity of the dorsal language pathway by stimulating either AL by recording CCEP from PL or vice versa, depending on stability and reproducibility of CCEP. We evaluated the first negative (N1) component of CCEP before, during, and after resection. RESULTS: All procedures were successfully completed without adverse events. The best response was obtained from AL during stimulation of PL in 8 patients and from PL during stimulation of AL in 6 patients. None of 12 patients with a postresection N1 amplitude decrease of 0%-15% from baseline presented postoperative language impairment. Decreases of 28% and 24%, respectively, of the N1 amplitude were observed in 2 patients who developed transient postoperative speech disturbances. CONCLUSIONS: The application of CCEP monitoring is possible and safe in epilepsy surgery under general anesthesia. Putative AL and PL can be identified using noninvasive presurgical neuroimaging. Decrease of N1 amplitude >15% from baseline may predict postoperative language deficits.
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Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/cirurgia , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Potenciais Evocados , Monitorização Neurofisiológica Intraoperatória/métodos , Transtornos da Linguagem/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Anestesia Geral , Criança , Pré-Escolar , Eletrodos , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Rede Nervosa , Complicações Pós-Operatórias/diagnóstico , Reprodutibilidade dos Testes , Distúrbios da Fala/etiologia , Adulto JovemRESUMO
BACKGROUND: Hippocampal sclerosis (HS) may be associated with focal cortical dysplasia IIIa (FCD IIIa) in patients undergoing surgery for temporal lobe epilepsy (TLE). OBJECTIVE: To investigate whether the anatomo-electro-clinical profile and surgical outcome in patients with HS-related TLE are affected by coexisting FCD IIIa. METHODS: A total of 220 patients, operated in 5 centers, with at least 24 mo follow-up (FU), were retrospectively studied. Preliminary univariate and subsequent multivariate analyses were performed to investigate possible associations between several potential presurgical, surgical, and postsurgical predictors and different variables (Engel's class I and Engel's class Ia, co-occurrence of FCD IIIa). RESULTS: At last available postoperative control (FU: range 24-95 mo, median 47 mo), 182 (82.7%) patients were classified as Engel's class I and 142 (64.5%) as Engel's class Ia. At multivariate analysis, extension of neocortical resection and postoperative electroencephalogram were significantly associated with Engel's class I, whereas length of FU had a significant impact on class Ia in the whole cohort and in isolated HS (iHS) patients, but not in the FCD IIIa group. No differences emerged in the anatomo-electro-clinical profile and surgical results between patients with FCD IIIa and with iHS. CONCLUSION: Coexistence of FCD IIIa did not confer a distinct anatomo-electro-clinical profile to patients with HS-related epilepsy. Postoperative seizure outcome was similar in FCD IIIa and iHS cases. These findings indicate limited clinical relevance of FCD IIIa in HS-related epilepsy and might be useful for refining future FCD classifications. Further studies are needed to clarify the correlation of class Ia outcome with the duration of FU.
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Encefalopatias/complicações , Epilepsia do Lobo Temporal/fisiopatologia , Epilepsia do Lobo Temporal/cirurgia , Malformações do Desenvolvimento Cortical/complicações , Adolescente , Adulto , Criança , Estudos de Coortes , Epilepsia do Lobo Temporal/etiologia , Feminino , Hipocampo/patologia , Humanos , Masculino , Análise Multivariada , Estudos Retrospectivos , Esclerose/complicações , Esclerose/patologia , Resultado do Tratamento , Adulto JovemRESUMO
Neuronal dendritic arborizations and dendritic spines are crucial for a normal synaptic transmission and may be critically involved in the pathophysiology of epilepsy. Alterations in dendritic morphology and spine loss mainly in hippocampal neurons have been reported both in epilepsy animal models and in human brain tissues from patients with epilepsy. However, it is still unclear whether these dendritic abnormalities relate to the cause of epilepsy or are generated by seizure recurrence. We investigated fine neuronal structures at the level of dendritic and spine organization using Golgi impregnation, and analysed synaptic networks with immunohistochemical markers of glutamatergic (vGLUT1) and GABAergic (vGAT) axon terminals in human cerebral cortices derived from epilepsy surgery. Specimens were obtained from 28 patients with different neuropathologically defined aetiologies: type Ia and type II focal cortical dysplasia, cryptogenic (no lesion) and temporal lobe epilepsy with hippocampal sclerosis. Autoptic tissues were used for comparison. Three-dimensional reconstructions of Golgi-impregnated neurons revealed severe dendritic reshaping and spine alteration in the core of the type II focal cortical dysplasia. Dysmorphic neurons showed increased dendritic complexity, reduction of dendritic spines and occasional filopodia-like protrusions emerging from the soma. Surprisingly, the intermingled normal-looking pyramidal neurons also showed severe spine loss and simplified dendritic arborization. No changes were observed outside the dysplasia (perilesional tissue) or in neocortical postsurgical tissue obtained in the other patient groups. Immunoreactivities of vGLUT1 and vGAT showed synaptic reorganization in the core of type II dysplasia characterized by the presence of abnormal perisomatic baskets around dysmorphic neurons, in particular those with filopodia-like protrusions, and changes in vGLUT1/vGAT expression. Ultrastructural data in type II dysplasia highlighted the presence of altered neuropil engulfed by glial processes. Our data indicate that the fine morphological aspect of neurons and dendritic spines are normal in epileptogenic neocortex, with the exception of type II dysplastic lesions. The findings suggest that the mechanisms leading to this severe form of cortical malformation interfere with the normal dendritic arborization and synaptic network organization. The data argue against the concept that long-lasting epilepsy and seizure recurrence per se unavoidably produce a dendritic pathology.
Assuntos
Córtex Cerebral/ultraestrutura , Dendritos/ultraestrutura , Espinhas Dendríticas/ultraestrutura , Epilepsia/patologia , Sinapses/ultraestrutura , Adolescente , Adulto , Córtex Cerebral/metabolismo , Pré-Escolar , Humanos , Lactente , Microscopia Eletrônica , Pessoa de Meia-Idade , Sinapses/metabolismo , Proteína Vesicular 1 de Transporte de Glutamato/metabolismo , Proteínas Vesiculares de Transporte de Aminoácidos Inibidores/metabolismo , Adulto JovemRESUMO
OBJECTIVE: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. METHODS: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons. RESULTS: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P = .006 and < .0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P = .023, Q = 0.046 vs normal, at 2-year FU and abnormal, improved, OR = 0.301, P = .001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P = .001, Q = 0.003, at 2-year FU and OR = 45.03, P < .0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. SIGNIFICANCE: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long-term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.